Epstein-Barr virus (EBV) is the etiologic agent of classical infectious mononucleosis. Its property of inducing cell transformation and its association with human neoplasms makes the study of this virus of prime importance. Although the intense lymphoproliferation that occurs in infectious mononucleosis resembles the acute phase of leukemia, the former disease is always or almost always self-limiting and benign in character. This self-limitation in vivo is in direct contrast of the capacity of the patient's lymphocytes to proliferate indefinitely in vitro as continuous cell lines with surface characteristics typical for B lymphocytes. The main objective of this study is to further define the mechanism responsible for the self-limited feature of the proliferation of abnormal lymphoid cells in patients with EBV induced infectious mononucleosis. Our preliminary results have demonstrated that there is a highly significant decrease in the number of IgM and IgD bearing cells during the acute phase of this disease. As convalescence proceeds, these changes, including a slight increase in T cells, return to normal. A larger number of individuals need to be evaluated to corroborate these findings and allow for adequate correlation between the lymphocyte subpopulation changes and the clinical manifestations or the prevalence and titer of antibodies to the various antigens of EBV. Likewise, studying the host's immune restraints to other forms of EBV infections, asymptomatic, symptomatic but with a noninfectious mononucleosis presentation and EBV reactivation has a potential for identifying important interrelationships between normal lymphocyte reactions and cancerous ones. Our preliminary results have shown that families of index cases of infectious mononucleosis are frequently concurrently experiencing these above mentioned forms of EBV activity and are thus an excellent source for study. The investigation described in this research proposal will document the immune response posed primarily by the human lymphocyte against a potential oncogenic viral infection. The findings from the present descriptive investigation will provide an important framework for future research regarding the functional interaction between EBV and B lymphocytes.